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增加剂量的甘氨酰谷氨酰胺用于多发伤患者全肠外营养的安全性和有效性

Safety and efficacy of increasing dosages of glycyl-glutamine for total parenteral nutrition in polytrauma patients.

作者信息

Weingartmann G, Fridrich P, Mauritz W, Götzinger P, Mittlböck M, Germann P, Karner J, Roth E

机构信息

Department of Medical Computer Sciences, AKH, University of Vienna.

出版信息

Wien Klin Wochenschr. 1996;108(21):683-8.

PMID:8956477
Abstract

Supplementation of parenteral nutrition with glutamine (GLN) has been suggested to improve the efficacy of nutritional support by stimulating protein synthesis and improving immunocompetence. In the present study we investigated the impact of infusing the dipeptide glycyl-glutamine (GLY-GLN) at increasing dosages on plasma amino acid concentrations in patients with polytrauma. Nine polytraumatized patients were randomly assigned according their age and their trauma score to three experimental groups. Group 1 received 280, group II 450, and group III 570 mg GLY-GLN per kg body weight/day for a period of four days (3rd to 7th posttraumatic day), resulting in a maximum daily GLN administration (calculated for a 70 kg patient) of 14 g, 21 g and 28 g, respectively. Seven polytraumatized patients receiving the nutrition solution without GLY-GLN supplementation served as controls. All patients received total parenteral nutrition with an average amino acid administration of 1.1 g/kg/day and a total energy intake of 30 kcal/kg/day. GLY-GLN infusion did not evoke any side effects. In comparison with the control group, arterial plasma GLN concentrations increased significantly on day I after start of infusion in groups II and III, but remained raised throughout the study period only in group III (p < 0.003). Similarly, plasma GLY concentrations were also significantly raised in group III (p < 0.04). The maximum increase of plasma GLY was found on the second infusion day, after which plasma concentrations of GLY fell to concentrations even below those observed in the control group at the end of the study period. Excretion of GLY-GLN, GLN or GLY in the urine during the GLY-GLN infusions was negligible. We conclude from this first available dose finding study on glutamine-containing dipeptides that in polytraumatized patients infusion of 570 mg/kg/day of GLY-GLN (corresponding to 28 g glutamine or 40 g dipeptide/70 kg, respectively) is necessary to induce a sustained effect on plasma glutamine concentrations. No pathological accumulation of free glycine or of the dipeptide was seen with any of the three dosage steps of GLY-GLN. Thus, the administration of even high doses of GLY-GLN is feasible and safe in patients with polytrauma and is not associated with any relevant renal substrate loss.

摘要

有人提出,肠外营养补充谷氨酰胺(GLN)可通过刺激蛋白质合成和提高免疫能力来提高营养支持的效果。在本研究中,我们调查了对多发伤患者输注不同剂量的二肽甘氨酰 - 谷氨酰胺(GLY - GLN)对血浆氨基酸浓度的影响。根据年龄和创伤评分将9名多发伤患者随机分为三个实验组。第一组每天每千克体重接受280毫克GLY - GLN,第二组为450毫克,第三组为570毫克,持续四天(创伤后第3天至第7天),这样对于一名70千克的患者,每日GLN的最大给药量(计算得出)分别为14克、21克和28克。7名未补充GLY - GLN的多发伤患者接受营养液作为对照。所有患者均接受全肠外营养,平均氨基酸给药量为每日1.1克/千克体重,总能量摄入量为每日30千卡/千克体重。输注GLY - GLN未引起任何副作用。与对照组相比,第二组和第三组在开始输注后第1天动脉血浆GLN浓度显著升高,但仅第三组在整个研究期间一直保持升高(p < 0.003)。同样,第三组血浆GLY浓度也显著升高(p < 0.04)。血浆GLY在第二次输注日达到最大增幅,之后在研究期末血浆GLY浓度降至甚至低于对照组观察到的浓度。在输注GLY - GLN期间,尿液中GLY - GLN、GLN或GLY的排泄量可忽略不计。从这项关于含谷氨酰胺二肽的首次剂量探索性研究中我们得出结论,对于多发伤患者,输注每日570毫克/千克体重的GLY - GLN(分别相当于28克谷氨酰胺或40克二肽/70千克体重)对于诱导血浆谷氨酰胺浓度产生持续影响是必要的。在GLY - GLN的三个剂量阶段中,均未观察到游离甘氨酸或二肽的病理性蓄积。因此,对多发伤患者给予甚至高剂量的GLY - GLN都是可行且安全的,并且与任何相关的肾脏底物损失无关。

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引用本文的文献

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Amino acids - Guidelines on Parenteral Nutrition, Chapter 4.氨基酸 - 肠外营养指南,第4章。
Ger Med Sci. 2009 Nov 18;7:Doc24. doi: 10.3205/000083.